PCSK9 inhibitor also effective and safe in children with HoFH?

Efficacy and safety of alirocumab in children and adolescents 2 with homozygous familial hypercholesterolemia: phase 3, 3 multinational open-label study

Literature - Bruckert E, Caprio S, Wiegman A, et al. - Arterioscler Thromb Vasc Biol. 2022;42:1447-57. doi: 10.1161/ATVBAHA.122.317793.

Introduction and methods


Despite advances in the treatment of patients with homozygous familial hypercholesterolemia (HoFH), most patients do not achieve target LDL-c levels with current lipid-modifying therapy [1]. Alirocumab is a human monoclonal antibody that selectively binds to PCSK9, a protein that plays a role in lipid homeostasis [2]. Alirocumab is indicated as an adjunct to diet in adults with primary hypercholesterolemia or mixed dyslipidemia, and for secondary prevention in established atherosclerotic CVD in adults [3,4]. However, this PCSK9 inhibitor is not approved for use in the pediatric population.

Aim of the study

This study examined the efficacy and safety of alirocumab in children with inadequately controlled HoFH.


The researchers conducted an international, multicenter, open-label, single-arm, phase 3 study in which 18 patients aged 8-17 years with HoFH received a subcutaneous injection of alirocumab 75 mg (body weight <50 kg) or 150 mg (body weight ≥50 kg) every 2 weeks for up to 48 weeks, in addition to background therapy, after a run-in period (≤4 weeks) and a screening period (≤2 weeks). Patients were eligible to participate if their disease was inadequately controlled despite optimal therapy with a statin and/or other lipid-modifying drugs at stable dose for ≥4 weeks. Patients with a null/null genotype for LDLR were excluded.


The primary outcome was the percent change in LDL-c levels from baseline to week 12. Secondary outcomes were: (a) the percent change in LDL-c levels from baseline to weeks 24 and 48; (b) the percent change in HDL-c, non-HDL-c, total cholesterol, triglyceride, apolipoprotein (Apo) A1 and B and lipoprotein a (Lp(a)) levels from baseline to weeks 12, 24 and 48; (c) the percentage of patients in whom LDL-c levels had decreased by ≥15% at weeks 12, 24 and 48; and (d) the absolute change in LDL-c levels from baseline to weeks 12, 24 and 48. Changes were expressed as least square mean. In addition, the safety of alirocumab was assessed.

Main results


  • At baseline, the mean LDL-c level was 373.0 mg/dL (SD: 193.5) and after week 12, it was decreased by 4.1% (SD: 36.0).
  • At weeks 24 and 48, LDL-c levels were decreased by 13.2 (SD: 28.5) and 0.4% (SD: 49.6), respectively.
  • During the follow-up period, mean absolute decreases in LDL-c levels ranged from 25-52 mg/dL.
  • The percentage of patients in whom LDL-c levels were decreased by ≥15% at weeks 12, 24 and 48 was 50.0, 52.9 and 41.2%, respectively.
  • Stratified by genotype, the response to alirocumab in patients demonstrated heterogeneity.

Other lipid parameters

  • Non-HDL-c, total cholesterol and ApoB levels were decreased at week 12 (3.9, 1.9 and 4.2%, respectively) and week 24 (9.2, 6.3 and 11.8%, respectively), but were increased at week 48 (0.9, 5.7 and 5.5%, respectively).
  • At all timepoints, HDL-c (8.9-13.0%), triglyceride (2.8-10.0%) and ApoA1 (11.3-14.6%) levels were increased from baseline.
  • In contrast, Lp(a) levels were decreased (5.2-7.4%) at all timepoints, compared with baseline.


  • Treatment-related adverse events occurred in 17 (94%) of patients, of which infections (n=7), respiratory, thoracic or mediastinal events (n=5) and cardiac events (n=4) were the most common.
  • One patient died, but the death was not treatment-related.
  • One patient developed a therapy-related, non-serious reaction at the injection site.


The results of this international, multicenter, open-label, phase 3 study suggest that subcutaneous injection of alirocumab every 2 weeks for up to 48 weeks is effective and safe in addition to other lipid-modifying therapy in children with inadequately controlled HoFH. There was heterogeneity in the response to alirocumab in lowering LDL-c, and the authors therefore highlight the importance of measuring LDL-receptor activity in addition to the genotype determination to decide on treatment strategies.


1. Cuchel M, Bruckert E, Ginsberg HN, et al; European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35:2146-57.

2. Tomlinson B, Patil NG, Fok M, et al. Role of pcsk9 inhibitors in patients with familial hypercholesterolemia. Endocrinol Metab (Seoul). 2021;36:279-95.

3. US Food and Drug Administration. Praluent (alirocumab) prescribing information; 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125559s002lbl.pdf.

4. European Medicines Agency. Praluent (alirocumab) summary of product characteristics; 2021. https://www.ema.europa.eu/en/documents/product-information/praluent-epar-product-information_en.pdf.

Find this article online at Arterioscler Thromb Vasc Bio.

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